This program is a continuation of a collaborative research effort between investigators at the Massachusetts Institute of Technology and the Massachusetts Eye and Ear Infirmary. Our program is multidisciplinary and combines state of the art laser and optical measurement technology with biomedical and medical research. Our objective is twofold: To explore new techniques to selectively enhance desired therapeutic laser tissue effects and to develop diagnostics of laser tissue interaction and microstructure in biological systems. The specific aims of this program are to: 1) Investigate ultrashort pulse laser induced optical breakdown as an approach for performing highly localized surgical incisions of intraocular structures using newly developed variable pulse duration and variable high repetition rate laser technology. Our investigation will include studies of fundamental physical incision and collateral damage using clinically relevant biological models in vitro. Applications to intraocular surgery will be explored using a vitreal membrane model and retinal injury studies in vivo. The basic premise of the ultrashort pulse scalpel is to use pulse duration to control collateral damage and multiple high repetition rate exposure to accumulate the desired effects of tissue incision. The development of an intraocular laser treatment capable of highly localized incisions with minimal collateral damage would have applications for a wide range of vitreal retinal conditions. 2) Develop optical ranging using coherence interferometry as a diagnostic for use either independently or in conjunction with intraocular laser surgery. This optical ranging technique is noncontacting, uses a compact laser diode source, requires low incident power levels (10 mu W) and provides a spatial resolution of 10 mum with sensitivity to reflected signals of 1 part in 1010. A clinically viable optical ranging device using fiber optic technology will be developed. Extensions of this technique such as scanning or using multiple wavelengths to distinguish differences in histological structure will be explored. Finally, optical ranging will be applied for measurements of retinal thickness and evaluated as a diagnostic for glaucoma using an animal model. The development of a noncontact method with superior resolution to ultrasound would permit real time monitoring of intraocular laser surgery and would have numerous medical diagnostic applications. 3) Finally as an extension of concepts demonstrated in our ultrashort pulse studies, we will perform pilot studies to explore methods for achieving highly localized thermal effects using multiple pulse exposure techniques with high power solid state IR lasers and dye enhanced absorption in a retinal vessel model.